On July 24, 2012, Prigioni signed a one-year contract with the New York Knicks for the rookie minimum.[5] At age 35, Prigioni became the oldest rookie in NBA history, when he made his debut on November 2, 2012. He became the team's starting point guard for the last two months of the 2012–13 season, as well as for the playoffs. In game 6 of the Knicks' first-round playoff series against the Boston Celtics, Prigioni made 3 three-pointers in the first quarter. The Knicks won 88–80, to advance to the second round of the playoffs for the first time in 13 years.[6]

On August 3, 2015, Prigioni signed with the Los Angeles Clippers.[10] On January 13, 2016, he had a career-high eight steals against the Miami Heat, which was one shy of the franchise record, held by his head coach, Doc Rivers.[11] On April 8, 2016, he recorded a season-high 13 points, a career-high seven rebounds, and a season-high seven assists, in a 102–99 overtime win over the Utah Jazz.[12]

On July 29, 2016, Prigioni signed with the Houston Rockets, returning to the franchise for a second stint.[13] However, he was waived by the Rockets on October 24, 2016, after appearing in five preseason games with them.[14]

On December 5, 2016, Prigioni returned to Baskonia, signing with them for the rest of the season.[15] He officially retired from his professional basketball playing career on January 9, 2017.[16][17] During his profesional career, Prigioni played in 10 EuroLeague seasons, in which he had career averages of 6.1 points, 4.3 assists, 2.5 rebounds, and 1.7 steals per game,[18] and in four NBA seasons, in which he had career regular season averages of 3.5 points, 2.8 assists, 1.9 rebounds, and 1.0 steals per game.[19]

On 16 June 2017, Prigioni began his coaching career, when he signed a two-year deal with Baskonia, to become their new head coach.[20] However, on October 26, Prigioni stepped down as Baskonia head coach, after having a 0–3 start in the EuroLeague and a 2–3 start in the Liga ACB.[21][22] On 24 April 2018, Prigioni joined the Brooklyn Nets as assistant coach.[23]